title: Deficiency of Dgcr8, a gene disrupted by the 22q11.2 microdeletion, results in altered short-term plasticity in the prefrontal cortex.
abstract: Individuals with 22q11.2 microdeletions have cognitive and behavioral impairments and the highest known genetic risk for developing schizophrenia. One gene disrupted by the 22q11.2 microdeletion is DGCR8, a component of the "microprocessor" complex that is essential for microRNA production, resulting in abnormal processing of specific brain miRNAs and working memory deficits. Here, we determine the effect of Dgcr8 deficiency on the structure and function of cortical circuits by assessing their laminar organization, as well as the neuronal morphology, and intrinsic and synaptic properties of layer 5 pyramidal neurons in the prefrontal cortex of Dgcr8(+/-) mutant mice. We found that heterozygous Dgcr8 mutant mice have slightly fewer cortical layer 2/4 neurons and that the basal dendrites of layer 5 pyramidal neurons have slightly smaller spines. In addition to the modest structural changes, field potential and whole-cell electrophysiological recordings performed in layer 5 of the prefrontal cortex revealed greater short-term synaptic depression during brief stimulation trains applied at 50 Hz to superficial cortical layers. This finding was accompanied by a decrease in the initial phase of synaptic potentiation. Our results identify altered short-term plasticity as a neural substrate underlying the cognitive dysfunction and the increased risk for schizophrenia associated with the 22q11.2 microdeletions.
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University Medical Center, New York, NY 10032, USA.
authors.forename: Karine
authors.initials: K
authors.lastname: Fénelon
authors.forename: Jun
authors.initials: J
authors.lastname: Mukai
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Pei-Ken
authors.initials: PK
authors.lastname: Hsu
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Drew
authors.forename: Maria
authors.initials: M
authors.lastname: Karayiorgou
authors.forename: Gerald D
authors.initials: GD
authors.lastname: Fischbach
authors.forename: Amy B
authors.initials: AB
authors.lastname: Macdermott
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Gogos
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000503:physiopathology; D056654:CA3 Region, Hippocampal / Q000503:physiopathology; D002872:Chromosome Deletion; D002892:Chromosomes, Human, Pair 22 / Q000235:genetics; D049229:Dendritic Spines / Q000378:metabolism / Q000473:pathology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D017353:Gene Deletion; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D017397:Prefrontal Cortex / Q000473:pathology / Q000503:physiopathology*; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins; D013569:Synapses / Q000378:metabolism; D013997:Time Factors
chemical_list: C474044:Dgcr8 protein, mouse; D011506:Proteins; D016601:RNA-Binding Proteins